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Saturday, May 26, 2012

Matt Ridley: How Dickensian childhoods leave genetic scars

Being maltreated as a child can perhaps affect you for life. It now seems the harm might reach into your very DNA. Two recently published studies found evidence of changes to the genetic material in people with experience of maltreatment. These are the tip of an iceberg of discoveries in the still largely mysterious field of "epigenetic" epidemiology-the alteration of gene expression in ways that affect later health.

According to standard theory, genes aren't supposed to change, so you can pass them on to generations untainted by your own mistakes. It now seems they can at least acquire marks of experience during life, affecting how much they are "expressed."
In one study, Avshalom Caspi, Terrie Moffitt and colleagues at Duke University and King's College London looked at sequences at the tips of chromosomes, known as telomeres, in 2,200 Britons born in 1994-95 and followed since birth. These telomeres contain repetitive sequences of DNA code "letters." The number of repeats shrinks during life in everybody, as a sort of clock for biological aging.

Studies had begun to suggest that psychosocial stress can speed up that clock by eroding telomeres more rapidly, though this research mostly relied on people's recall of maltreatment. Then Stacy Drury and colleagues at Tulane University found shorter telomeres in children who stayed in Bucharest orphanages, compared with those in foster families.

The Duke scientists have measured the effect of exposure to bullying, beating or domestic violence between the mother and her partner on telomere length between the ages of 5 and 10. Because blood samples had been taken from the Britons throughout life, it was possible to compare telomere length before and after the violence was experienced. On average, the telomeres did shrink faster in those that experienced violence than in other children.

But in some individuals they actually grew longer, so the mystery of telomeres only deepens. The next step, Dr. Moffitt told me, is to assess subjects' later health by measuring such things as memory changes, inflammation, immune function, even tooth decay. She adds: "So wish us luck!"

Another study, published earlier this year by Audrey Tyrka of Butler Hospital, Providence, R.I., and others found that the loss of a parent or maltreatment as a child resulted in greater "methylation" of some spots near a gene tied to stress response in adulthood. Methylation, the addition of a methyl group of atoms to one DNA "letter," tends to reduce the activity of nearby genes. The implication of the Butler study is that adults who recall maltreatment as children may have reduced activity of a key gene in the system that responds to the stress hormone cortisol. This may be linked to increased anxiety or depression.

These are early days in the study of epigenetics. Scientists are like people finding coins under lampposts but not knowing how many coins remain in the dark. Although the "methylome"-a complete map of where methylation happens in the genome-is being talked of, others caution that we still have almost no idea of both the causes and effects of most such changes, let alone other epigenetic effects like histone modification.

But supposing it does become possible to link bad early experience with bad later health, what then? Epigenetics demolishes the old-and always misleading-distinction between deterministic genes and a manipulable environment. To have your fate determined by your early experiences is not much different from having it determined by your genes, and when experience acts by changing genes, the distinction vanishes.

Yet fortunately, given medical advances, genetic determinism is not necessarily a life sentence, as those who wear glasses for shortsightedness or take growth hormone for growth problems can attest. The same will almost certainly be true for epigenetic determinism: Understanding the mechanism should bring forward possible cures.

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